JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
·
2019
·
IF 2.983
Qingqing Yang,Jing Sun,Chuan Li,Haizhi Zhang,Weiren Xu,Changxiao Liu,Xuemin Zheng
Specific study about the effect of cytochrome P450 2D6 (CYP2D6) polymorphisms on the metabolism of clinic drugs is of great significance for drug safety investigation. Here, the interaction between CYP2D6 variants (*1, *2, *10, *39) and metoprolol (MET) was intensively researched in vitro from the aspect of drug-enzyme kinetic study. To obtain quantitative data, α -hydroxymetoprolol (main metabolite of MET) was selected as an ideal analyte and an LC–MS/MS method was adopted for sample determination. Firstly, by selecting suitable internal standard and optimizing separation condition, the LC–MS/MS method was established and validated. Then, the drug-enzyme incubation system was optimized by two parameters: incubation time and amount of enzyme. Lastly, the interaction between CYP2D6 allelic variants and MET was characterized by K m , V max and CL int . As a result, four CYP2D6 enzymes displayed diverse K m or V max towards MET and the values of CL int showed a wide range from 8.91 to 100%. Relative to CYP2D6*1 (CL int *1 = 100%), CYP2D6*2 demonstrated the second high catalytic activity (CL int *2/*1 = 74.87%) while CYP2D6*39 (CL int *39/*1 = 29.65%) and CYP2D6*10 (CL int *10/*1 = 8.91%) showed minimal catalytic activity. This comprehensive in vitro data suggested the prominent influence of CYP2D6 polymorphisms on the metabolism of MET, which could offer valuable information for personalized administration of MET in clinic.
研究领域:
药理学
·
临床医学
·
生物化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
SCIENCE OF THE TOTAL ENVIRONMENT
·
2021
·
IF 7.963
Yuan He,Liangjie Wang,Zhan Chen,Bo Shen,Jinshan Wei,Ping Zeng,Xianghua Wen
Manganese dioxide has been widely recognized as catalyst in catalytic ozonation for organic pollutants removal from wastewater in recent decades. However, few studies focus on the structure-activity relationship of MnO 2 and catalytic ozonation mechanism in water. In the present study, the oxidative reactivity of three different crystal phases of MnO 2 corresponding to α-MnO 2 , β-MnO 2 and γ-MnO 2 towards metoprolol (MET) and ibuprofen (IBU) were evaluated. α-MnO 2 was found to contain the most abundant oxygen vacancy and readily reducible surface adsorbed oxygen (O 2− , O − , OH − ), which facilitated an increase of ozone utilization and the highest catalytic performance with 99% degradation efficiency for IBU and MET. α-MnO 2 was then selected to investigate the optimum key operating parameters with a result of catalyst dosage 0.1 g/L, ozone dosage 1 mg/min and an initial pH 7. The introduction of α-MnO 2 promoted reactive oxygen species (O 2− , O − , OH − ) generation which played significant roles in IBU degradation. Probable degradation pathways of MET and IBU were proposed according to the organic intermediates identified and the reaction sites based on density function theory (DFT) calculations. The present study deepened our understanding on the MnO 2 catalyzed ozonation and provided reference to enhance the process efficiency.
研究领域:
环境科学
·
化学工程
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF HAZARDOUS MATERIALS
·
2024
·
IF 12.2
Sui-Qin Yang,Rui-Qiu Ye,Yu-Hong Cui,Zheng-Qian Liu,Kai Sun,Yu-Ze Yu
Advanced oxidation processes for the treatment of organic pollutants in wastewater suffer from difficulties in mineralization, potential risks of dissolved residues, and high oxidant consumption. In this study, radical-initiated polymerization is dominated in an UV/peroxydisulfate (PDS) process to eliminate organic pollutant of pharmaceutical metoprolol (MTP). Compared with an ideal degradation-based UV/PDS process, the present process can save four fifths of PDS consumption at the same dissolved organic carbon removal of 47.3%. Simultaneously, organic carbon can be recovered from aqueous solution by separating solid polymers at a ratio of 50% of the initial chemical oxygen demand. The chemical structure of products was analyzed to infer the transformation pathways of MTP. Unlike previous studies on simple organic pollutants that the polymerization can occur independently, the polymerization of MTP is dependent on the partial degradation of MTP, and the main monomer in polymerization is a dominant degradation product (4-(2-methoxyethyl)-phenol, denoted as DP151). The separated solid polymers are formed by repeated oxidation and coupling of DP151 or its derivatives through a series of intermediate oligomers . This proof-of-concept study demonstrates the advantage of polymerization-dominated mechanism on dealing with large organic molecules with complex structures, as well as the potential of UV/PDS process for simultaneous organic pollution reduction and organic carbon recovery from aqueous solution.
研究领域:
环境科学
·
水处理工程
·
药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
RSC Advances
·
2020
·Vol. 10
·期 35
·20991-20999
·
IF 3.119
Yu-qiong Gao,Jia Zhang,Jin-qiang Zhou,Cong Li,Nai-yun Gao,Da-qiang Yin
In this study, nano zero-valent iron (nZVI) was utilized to activate persulfate (PS) for the degradation of metoprolol (MTP), a commonly used drug for curing cardiovascular diseases, in water. Quenching tests indicated that both the sulfate radical (SO4˙−) and hydroxyl radical (˙OH) contributed to the degradation of MTP, while SO4˙− seemed to play a large role under natural pH conditions. Batch tests were conducted to investigate the effects of several influencing factors, such as PS concentration, initial MTP concentration, pH, temperature and common anions, on the degradation performance of MTP. Generally, lower MTP concentration and pH values, and higher PS concentration and temperature favoured MTP degradation. HCO3−, NO3− and SO42− were found to inhibit MTP degradation, while Cl− enhanced MTP degradation. Several corrosion products of nZVI, including Fe3O4, Fe2O3 and FeSO4, were formed during the reaction, which was reflected by the combined XRD and XPS analysis. Degradation pathways of MTP were proposed according to the identified transformation products, and the peak areas of the major products along with the time were also monitored. Finally, the toxicity of the reaction solution was assessed by experiments using Aliivibrio fischeri. Overall, it could be concluded that nZVI/PS might be a promising method for the rapid treatment of MTP-caused water pollution.
研究领域:
环境科学
·
水处理技术
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产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING SCIENCE
·
2017
·
IF 2.895
Panliang Zhang,Shichuan Wang,Kewen Tang,Weifeng Xu,Fan He,Yunren Qiu
Enantioselective extraction of metoprolol (MT) enantiomers with di-cyclohexyl (D)-tartrate (DT) and boric acid (BA) as chiral extractant was performed. The process involving multiple chemical equilibrium is very complicated and the process optimization is difficult. On the basis of an interfacial reaction mechanism, a single-stage extraction model was established. The operation conditions of pH and DT to BA ratio were obtained through simulation and optimization of the equilibrium of the two phase extraction system. Based on the single-stage extraction model and the law of mass conservation, a fractional extraction model was established to simulate and optimize the fractional extraction process. To pursue a high productivity and reduce the required stages, a high feed to aqueous phase ratio (F/W = 1) and an asymmetric separation mode were applied. By asymmetric separation where the optical purity of the product in extract phase and raffiniate phase is not equal, enantiomeric excess ( ee ) value for the eutomer of MT can reach up to 98.64% and yield can reach up to 64.68% with 20 extraction stages.
研究领域:
化学工程
·
制药工程
✓ 已验证
产品关联
DOI
高影响因子
CURRENT DRUG METABOLISM
·
2022
·Vol. 23
·期 2
·131-136
·
IF 3.408
Shi Zhongbo,Jiang Junhao,Zhao Dezhang,Xie Baogang,Li Yan,Yu Chao
Backgrond: Astragaloside IV (AST) and metoprolol are often used together to treat cardiovascular diseases, while the herb-drug interaction (HDI) between them is still unclear. Objective: This study investigates the effect of AST on the pharmacokinetics of metoprolol in rats and
its mechanism to predict the HDI. Method: First, IC50 value of AST on nine CYP450 enzymes in human liver microsomes (HLMs) was determined by the cocktail method. We explored the effect of AST on the pharmacokinetics of metoprolol (metabolized by CYP2D6) in vivo. Twelve male SD rats were
equally divided into two groups, with or without pretreatment of AST (3 mg/kg/day) for 7 days, and they received metoprolol (27 mg/kg) by oral administration. Blood samples were determined using HPLC. Finally, the mechanism of AST was explored. Results: AST exhibited a moderate inhibitory
effect on CYP2D6 with IC50 value of 32.28 μM. The pharmacokinetic parameters of metoprolol were significantly altered by AST with the increase of AUC0-∞ (538.81 ± 51.41 to 1088.34 ± 86.46 μg*min/mL, P<0.05) and Cmax
(6.21 ± 0.56 to 8.34 ± 0.87 μg/ml, P<0.05). The investigation of the mechanism showed AST to be an irreversible inhibitor of CYP2D6 with KI value of 2.9 μM and Kinact of 0.018 min−1, respectively.
Conclusion: AST was found to increase the plasma exposure of metoprolol in rats. AST reduced the metabolism of metoprolol by inhibiting CYP2D6 activity. The HDI might enhance when metoprolol and AST will be applied in combination.
研究领域:
药理学
·
临床医学
·
生物化学
✓ 已验证
DOI
PubMed
高影响因子
Journal of Environmental Chemical Engineering
·
2023
·
IF 7.7
Junjian Zheng,Jiaqi Wei,Shaoping Xu,Yuanyuan Zhang,Xueye Wang,Zhiwei Wang
Electrochemical membrane filtration (EMF) is a promising advanced oxidation technology for eliminating aquatic refractory pharmaceuticals. In this work, three porous foam-titanium based metal oxide (MO x) anodic membranes were prepared for comparison of their effectiveness against the model pharmaceutical pollutant metoprolol. The electrooxidation efficiencies of metoprolol by all flow-by operated anodic membranes were found to be elevated with increasing charging voltage and decreasing electrolyte solution pH, in which the PbO 2 membrane exhibited more efficient metoprolol degradation efficiency over SnO 2 and RuO 2 membranes. At the chosen charging voltage of 2 V and electrolyte solution pH 7, compared to the flow-by mode, the higher total organic carbon (TOC) removal and less electrical energy consumption was achieved by the flow-through operated PbO 2 membrane, ascribed to the enhanced mass-transfer of metoprolol and its intermediate by-products toward the anode surface. The physisorbed and free HO • produced by PbO 2 membrane were found to be the key oxidants accounting for metoprolol degradation, which induced the transformation of metoprolol by attacking its benzene ring and side chains. Apart from the capacity for detoxifying metoprolol-containing influent, PbO 2 membrane also exhibited favorable stability in flow-through mode. The study provides an effective strategy for the electrochemical remediation of pharmaceutical-polluted water and wastewater.
研究领域:
环境科学
·
药学
·
材料科学
✓ 已验证
产品关联
DOI
高影响因子
Environmental Chemistry Letters
·
2018
·Vol. 16
·期 2
·599-603
·
IF 3.125
Chen Long,Luo Tao,Yang Shaojie,Xu Jing,Liu Zizheng,Wu Feng
Metal/sulfite systems are currently used for SO
•− 4
generation and oxidative removal of organic contaminants. However, homogeneous metal/sulfite systems are limited because their working pHs must be acidic and metal ions cannot be separated from the bulk reaction solution. As a consequence, these drawbacks have severely limited the application of metal/sulfite systems in real conditions. To address these issues, we tested the use of copper ferrite (CuFe 2 O 4 ), a ferromagnetic nanoparticle, to catalyze sulfite oxidation for the degradation of the metoprolol drug. The reaction mechanism was investigated by electron spin resonance, X-ray photoelectron spectroscopy, and radical quenching assay. The effects of pH, CuFe 2 O 4 , and sulfite dosages were also assessed. Results show that SO
•− 4
was the primary radical responsible for metoprolol degradation. Higher pHs induced more metoprolol degradation using CuFe 2 O 4 /sulfite. Moreover, CuFe 2 O 4 remained morphologically intact and catalytically active after four batches of recycling. Overall, our findings show that CuFe 2 O 4 /sulfite can effectively degrade water contaminants in alkali pH and withhold catalyst activity after multiple reuses, therefore addressing the issues associated with homogeneous metal/sulfite systems.
研究领域:
环境科学
·
材料科学
·
化学
✓ 已验证
产品关联
DOI
高影响因子
DRUG DEVELOPMENT AND INDUSTRIAL PHARMACY
·
2017
·
IF 2.295
Yan Yang,Lian Shen,Juan Li,Wei-guang Shan
The objective of this study was to prepare and evaluate metoprolol tartrate sustained-release pellets. Cores were prepared by hot melt extrusion and coated pellets were prepared by hot melt coating. Cores were found to exist in a single-phase state and drug in amorphous form. Plasticizers had a significant effect on torque and drug content, while release modifiers and coating level significantly affected the drug-release behavior. The mechanisms of drug release from cores and coated pellets were Fickian diffusion and diffusion–erosion. The coated pellets exhibited sustained-release properties in vitro and in vivo.
研究领域:
药剂学
·
药物传递系统
·
制药工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Environmental Sciences
·
2022
·
IF 6.796
Ying Cao,Juan Li,Yanxin Zhao,Yumeng Zhao,Wei Qiu,Suyan Pang,Jin Jiang
The degradation of metoprolol (MTP) by the UV/sulfite with oxygen as an advanced reduction process (ARP) and that without oxygen as an advanced oxidation process (AOP) was comparatively studied herein. The degradation of MTP by both processes followed the first-order rate law with comparable reaction rate constants of 1.50 × 10 − 3 se c − 1 and 1.20 × 10 − 3 se c − 1 , respectively. Scavenging experiments demonstrated that both e aq − and H • played a crucial role in MTP degradation by the UV/sulfite as an ARP, while SO 4 • − was the dominant oxidant in the UV/sulfite AOP. The degradation kinetics of MTP by the UV/sulfite as an ARP and AOP shared a similar pH dependence with a minimum rate obtained around pH 8. The results could be well explained by the pH impacts on the MTP speciation and sulfite species. Totally six transformation products (TPs) were identified from MTP degradation by the UV/sulfite ARP, and two additional ones were detected in the UV/sulfite AOP. The benzene ring and ether groups of MTP were proposed as the major reactive sites for both processes based on molecular orbital calculations by density functional theory (DFT). The similar degradation products of MTP by the UV/sulfite process as an ARP and AOP indicated that e aq − / H • and SO 4 • − might share similar reaction mechanisms, primarily including hydroxylation, dealkylation, and H abstraction. The toxicity of MTP solution treated by the UV/sulfite AOP was calculated to be higher than that in the ARP by the Ecological Structure Activity Relationships (ECOSAR) software, due to the accumulation of TPs with higher toxicity.
研究领域:
环境科学
·
化学工程
✓ 已验证
DOI
PubMed
高影响因子
CHEMICAL RESEARCH IN TOXICOLOGY
·
2022
·
IF 3.973
Xiaonan Li,Gang Xing,Xinxin Guo,Yang Wang,Zixia Hu,Maosheng Cheng,Ying Peng,Jiang Zheng
As a selective β1-receptor antagonist, metoprolol tartrate (MTA) is commonly used to treat cardiovascular diseases such as hypertension and angina pectoris. There have been cases of liver injury induced by MTA, but the mechanism of hepatotoxicity induced by MTA is not clear. The purposes of this study were to identify the reactive metabolites of MTA, to determine the pathway for the metabolic activation of MTA, and to define a possible correlation between the metabolic activation and cytotoxicity of MTA. Three oxidative metabolites (M1–M3), a glutathione (GSH) conjugate (M4), and an N-acetyl cysteine (NAC) conjugate (M5) were detected in rat liver microsomal incubations containing MTA and GSH or NAC. M4 was also detected in cultured rat primary hepatocytes and bile of rats given MTA, and M5 was detected in the urine of MTA-treated rats. A quinone methide intermediate may be produced from the metabolic activation process in vitro and in vivo. The metabolite was reactive to glutathione and N-acetyl cysteine. MTA induced marked cytotoxicity in cultured rat primary hepatocytes. Pretreatment of aminobenzotriazole, a nonselective P450 enzyme inhibitor, attenuated the susceptibility of hepatocytes to MTA cytotoxicity.
研究领域:
药理学
·
毒理学
·
医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF SEPARATION SCIENCE
·
2020
·Vol. 43
·期 11
·2193-2200
·
IF 2.878
Lei Xu,Weiqi Meng,Jing Lu,Fengjuan Cui,Lidi Gao,Lin Chen,Yang Xin
A sensitive approach of capillary electrophoresis coupled with field-amplified sample injection and transient isotachophoresis was developed for the simultaneous determination of two β-blockers: sotalol and metoprolol. In this dual focusing technique, the samples were prepared via only dissolution in ultrapure water and then injected electrokinetically. Phosphate acted as both the background electrolyte and the leading electrolyte. Its optimized concentration was 80 mM. A total of 25 mM of glycine was used as the terminating electrolyte. Under optimum conditions, good separation of sotalol and metoprolol was achieved within 10 min. In comparison with the conventional method, the sensitivity enhancement factors were up to 1031 and 919 for sotalol and metoprolol, respectively. The proposed method was employed in the determination of sotalol and metoprolol in spiked human urine samples. The limits of detection and limits of quantitation obtained via ultraviolet detection were 5 and 12 ng/mL, respectively, for sotalol, and 10 and 25 ng/mL, respectively, for metoprolol. The intraday repeatability values were lower than 2.7 and 1.7% for peak area and migration time, respectively. The assay is a simple and efficient strategy with potential for application in clinical and biochemical laboratories for monitoring sotalol and metoprolol.
研究领域:
分析化学
·
临床医学
·
药理学
✓ 已验证
DOI
高影响因子
危险品化学品经营许可证（带存储）